The long-term goal of the Northern New England Clinical and Translational Research Network (NNE-CTR), composed of MaineHealth, the University of Vermont, and the University of Southern Maine, is to sustain a clinical and translational research infrastructure that supports improvements in community health for northern New England inhabitants. Maine and Vermont have the oldest populations in the U.S. and that, coupled with rurality, predisposes residents to a range of disorders ranging from cancer to substance use disorders, food insecurity, obesity, diabetes and cardiovascular disease. We are addressing these health challenges by linking primary care practice centers with academic centers and developing innovative approaches to community-based research. During our first four years, the NNE-CTR has built a strong foundation for clinical research. We partnered with the oldest regional practice-based research network (PBRN), the Dartmouth Co-Op, and actively supported successful NIH program applications, including two COBREs, two NCI program grants, an infrastructure grant for a new Center for Biomedical Shared Resources, and a HRSA grant to build on the opioid treatment model pioneered in Vermont. The NNE-CTR PI is playing a leadership role in coordinating a national CTR network, including the CTR National COVID Cohort Collaborative (N3C), a registry to share clinical data on Covid-19 nationally, and the NIH-sponsored RECOVER trial, which will define the long-term sequelae of Covid-19. In this renewal, we plan to expand our collaborations both regionally and nationally and strengthen our PBRN. We will strengthen Core resources that include: the Biostatistics, Epidemiology and Research Design Core, which will improve data capability and research navigation services; the Professional Development Core, which will offer an array of new educational and mentorship opportunities; the Pilot Projects Program, which will provide new and flexible funding mechanisms to offer more support for community-based projects; the Translational Research and Technology Core, offering state-of-the-art technologies and training for new investigators, and the Community Engagement and Outreach Core, which will build stronger bridges to communities. We propose three specific aims: 1-Expand infrastructure and resources to address clinical and translational research needs in northern New England; 2- Strengthen clinical and translational research that expands clinical trial access, telehealth, and mentored training programs for new investigators; and 3-Accelerate regional and national collaborative initiatives within the IDeA networks and through NIH such as N3C and RECOVER.